Elucidation of pathogenic mechanism of autoimmune pituitary disease and clinical application

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kobe University
• Principal Investigator: Iguchi Genzo 神戸大学, 保健管理センター, 准教授 (60346260)
• Co-Investigator(Kenkyū-buntansha): 高橋 裕 神戸大学, 医学研究科, 准教授 (70301281)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 自己免疫性下垂体疾患 / 抗PIT-1下垂体炎 / 腫瘍随伴症候群

Outline of Final Research Achievements

Elucidation of pathogenic mechanism of autoimmune pituitary disease: Ectopic expression of PIT-1 and infiltration of cytotoxic T cells were observed in the tumor tissue of patients with anti-PIT-1 hypophysitis, indicating that this disease has an aspect as a paraneoplastic syndrome caused by a malignant tumor. The clinical features of isolated ACTH deficiency were classified into three types by adding anti-pituitary antibody analysis, and the true nature of their diversity and the etiology and pathophysiology were clarified. As a tool for analyzing the molecular mechanism of autoimmune pituitary disease, using anti-PIT-1 hypophysitis as a model, we established Pit-1 specific cytotoxic T cell clone and co-cultured it with the patient's iPS cell-derived pituitary gland. As a result, we have succeeded in creating the first in vitro human autoimmune disease model.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまで原因が不明であった自己免疫性下垂体疾患の発症メカニズムを多面的に解明した。抗PIT-1下垂体炎が胸腺腫瘍だけでなく悪性腫瘍の患者において発症することを明らかにし、新たな臨床情報をもたらした。ACTH単独欠損症において新たな臨床分類を提唱したことにより、病因に応じた詳細な機序の解明や治療法の選択の可能性へとつながった。さらに、自己免疫性下垂体疾患は疾患モデルがないことが壁となっていたが、世界初のヒトのin vitro自己免疫疾患モデル作成に成功したことにより、本モデルを用いたさらなる解析へと発展することが期待される。